Chromatin architecture reprogramming reveals novel epigenetic dependencies in breast cancer
Year: 2025
Type: preprint
Abstract: Chromatin architecture plays a key role in development and cancer, yet most studies lack mechanistic depth due to widespread epigenomic remodeling. To address this, we tracked chromatin structure dynamics during the progression of endocrine resistance in ER + breast cancer using Hi-C, chromatin accessibility, epigenomic, and transcriptomic profiling. We uncovered a critical role for H3K9 methylation and the demethylase KDM4C association with SWI/SNF in driving proliferation of cells fated to become resistant through a nongenomic estrogen-mediated mechanism. These findings highlight the mechanistic contribution of chromatin regulation in therapy resistance and offer a blueprint for studying similar processes in cancer, development, and cell fate decisions.
Source: Genes & Development
Authors: Liliana Garcia-Martinez, Mengsheng Zha, Rodrigo L. Borges, Tong Liu, Gretter González-Blanco, Alana Martinez Alonso, Stephanie Stransky, Simone Sidoli, Hao Zhu, Zheng Wang, Lluis Morey
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Awards: G1107474982, G1238997801, Advanced algorithms to infer and analyze 3D genome structures, G4251119674, G427533880, G4760172412, Epigenetic dependencies and vulnerabilities in endocrine-resistant breast cancer, Mechanisms of RING1B and PRC1 complexes in transcriptional activation, Altering the chromostasis and genome stability by modulating histone methylation
OpenAlex ID: W4417475732